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Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

By Ribeiro Ricardo, Monteiro Cátia, Catalán Victoria, Hu Pingzhao, Cunha Virgínia, Rodríguez Amaia, Gómez-Ambrosi Javier, Fraga Avelino, Príncipe Paulo, Lobato Carlos, Lobo Francisco, Morais António, Silva Vitor, Sanches-Magalhães José, Oliveira Jorge, Pina Francisco, Lopes Carlos, Medeiros Rui and Frühbeck Gema

Abstract

<p>Abstract</p> <p>Background</p> <p>Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients.</p> <p>Methods</p> <p>Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks.</p> <p>Results</p> <p>In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, <it>FADS1</it>, down-regulated, and <it>LEP </it>and <it>ANGPT1</it>, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of <it>CFH</it>). Interestingly, we found that the microRNA <it>MIRLET7A2 </it>was overexpressed in the PP adipose tissue of prostate cancer patients.</p> <p>Conclusions</p> <p>Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.</p

Topics: adipose tissue, gene expression, microarray, obesity, periprostatic, prostate cancer, Medicine (General), R5-920, Medicine, R, DOAJ:Medicine (General), DOAJ:Health Sciences
Publisher: BioMed Central
Year: 2012
DOI identifier: 10.1186/1741-7015-10-108
OAI identifier: oai:doaj.org/article:1420b2020d7b43238cb17aeb5e991b2a
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